POS1390 ULTRASOUND BASED WITHDRAWAL OF BIOLOGICS IN RHEUMATOID ARTHRITIS (RA-BioStop)
Authors: C. Dejaco, I. Gessl, R. Husic, T. Deimel, A. Lackner, G. Supp, J. Hermann, J. S. Smolen, M. Stradner, D. Aletaha, G. Schwantzer, P. Mandl
Journal: Annals of the Rheumatic Diseases (2022)

Background Discontinuation of biological (b)DMARDs may be considered in rheumatoid arthritis (RA) patients in persistent clinical remission [1]. Some earlier studies reported that baseline ultrasound may predict successful tapering or withdrawal of bDMARDs, while others found that ultrasound had little additional value over clinical parameters alone [2-4]. The majority of these studies, however, were limited by small sample size, inadequate remission criteria and variable tapering regimens. Objectives To test the hypothesis whether ultrasound-verified subclinical inflammation might predict a relapse in RA patients in stringent clinical remission who discontinue bDMARDs. Methods Prospective, phase IV clinical trial including RA patients in persistent clinical remission according to the ACR/EULAR criteria treated with a combination of conventional synthetic (cs)DMARD plus bDMARDs. Upon stopping the bDMARD, 9 study visits were conducted within 52 weeks. At each visit, patients underwent clinical examination and ultrasound of 14 joints. The primary hypothesis was that a Power Doppler (PD) score &gt;0 predicted a relapse until week 16 after bDMARD cessation. Relapse was defined as change from remission to moderate/high disease activity according to the simplified disease activity index. Results Although 110 patients were required by the protocol, inclusion had to be stopped after reaching 38 (34.5%) due to insufficient recruitment. There were 9, 10 and 13 relapses between baseline and weeks 16, 24 and 52, respectively. Relapses till week 16 tended to be more common in patients with PD score &gt;0 at baseline than in those without [9/30 (30.0%) vs. 0/7 (0%), p=0.160)]. Similar observations were made for weeks 24 [9/30 (30.0%) vs. 1/7 (14.3%), p=0.647)] and 52 [12/30 (40.0%) vs. 1/7 (14.3%), p=0.383)]. Kaplan-Meier plot indicates the relapse-free survival in patients with and without PD+ synovitis at baseline (Figure 1). Figure 1. Kaplan-Meier analysis of relapses according to presence or absence of Power Doppler (PD) synovitis at baseline. PD scores were higher at the time of relapse as compared to the preceding visits [mean difference in the PD score 3.2 (±4.5) points, p=0.034]. PD scores were also higher at visits preceding a relapse [mean 5.6 (±3.9), n=13] as compared to the mean PD score across all visits of patients without a relapse [mean 2.0 (±1.5), n=24, p=0.003, respectively]. There were trends towards a higher mean baseline PD score in patients who had a relapse between baseline and week 16 as compared to those who remained in remission (5.2 ± 5.8 vs. 2.3 ± 3.0, p=0.079). Similar observations were made for relapses until weeks 24 and 52. No difference was observed comparing mean residual swollen or tender joint counts at baseline between patients with and without a relapse. There were 9 adverse events. All of them were mild to moderate. Conclusion In RA patients in strict clinical remission, PD assessment at baseline but not clinical joint count could help identify patients who will relapse after the cessation of a bDMARD. Due to insufficient recruitment and limited power of the present trial, however, no definitive conclusion can be made. References [1]Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020; 79 :685-99. [2]Naredo E, Valor L, De la Torre I, et al. Predictive value of Doppler ultrasound-detected synovitis in relation to failed tapering of biologic therapy in patients with rheumatoid arthritis. Rheumatology (Oxford ) 2015; 54 :1408–14. [3]Lamers-Karnebeek FB, Luime JJ, Cate DFT, et al. Limited value for ultrasonography in predicting flare in rheumatoid arthritis patients with low disease activity stopping TNF inhibitors. Rheumatology (Oxford ) 2017; 56 :1560–5. [4]Terslev L, Brahe CH, Hetland ML, et al. Doppler ultrasound predicts successful discontinuation of biological DMARDs in rheumatoid arthritis patients in clinical remission. Rheumatology (Oxford ) 2021; 60 :5549–59. Acknowledgements This study was funded by a grant of the Austrian Research Fund (KLI514-B30) Disclosure of Interests Christian Dejaco Speakers bureau: Pfizer, AbbVie, MSD, Roche, BMS, UCB, Consultant of: Pfizer, AbbVie, MSD, Roche, BMS, UCB, Grant/research support from: Pfizer, Irina Gessl: None declared, Rusmir Husic Speakers bureau: MSD, Lilly und Abbvie, Thomas Deimel: None declared, Angelika Lackner: None declared, Gabriela Supp: None declared, Josef Hermann Speakers bureau: Novartis, Lilly, AbbVie, Janssen, Consultant of: GlaxoSmithKline, Otsuka Pharmaceutical Europe Ltd, Josef S. Smolen Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, Merck Sharp &amp; Dohme, Novartis- Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB, Consultant of: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, Merck Sharp &amp; Dohme, Novartis- Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB, Grant/research support from: Abbvie, AstraZeneca, Lilly and Roche, Martin Stradner Speakers bureau: Eli Lilly, Pfizer, MSD, BMS, AbbVie, Janssen, Consultant of: Eli Lilly, AbbVie, Janssen, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Consultant of: Abbvie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, Gerold Schwantzer: None declared, Peter Mandl Speakers bureau: AbbVie, Janssen and Novartis, Grant/research support from: AbbVie, BMS, Novartis, Janssen, MSD and UCB